The Supramolecular Organization Of Cancer Metabolism
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The Supramolecular Organization Of Cancer Metabolism
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Author : Cristina Balcells Nadal
language : en
Publisher:
Release Date : 2020
The Supramolecular Organization Of Cancer Metabolism written by Cristina Balcells Nadal and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2020 with categories.
"Metastasis and drug resistance represent the two main causes of therapeutic failure in oncology. In the present dissertation, the interplay between them has been interrogated using metabolomics, systems biology and biophysical approaches, in an attempt to find common phenotypic adaptations and metabolic vulnerabilities of metastatic and resistant cancer cells, potentially exploitable in novel combination therapies. The obtained results unveil that highly metastatic e-CSC phenotypes of CRPC present particular metabolic vulnerabilities that can potentially lead to establishing putative biomarkers and metabolic targets that are specific for PCa subsets with high tumorigenic potential. Moreover, by generating isogenic cell models of multiplatinum resistance in CRPC and CRC we also identified that metastatic solid tumors with originally opposed metabolic profiles can lead to different metabolic adaptations as they acquire platinum resistance, but that a common metabolic signature of acquired platinum resistance arises, which also includes alterations in proline and one carbon metabolism, glutathione synthesis and ROS production. In addition to characterizing in deep the metabolic reprogramming associated to resistance to platinum compounds already used in the clinics, we also explored the possibility to design of novel platinum drugs able to counter platinum-resistant tumors. In this regard, we identified novel families of cyclometallated platinum (II) and platinum (IV) compounds exhibit strong antiproliferative effects in the low micromolar range against a wide variety of solid tumors. The leading compounds of each series also exhibit remarkable selectivity for cancer cells and the capacity to arrest the cell cycle at S and G2/M phases, induce apoptosis and increase intracellular ROS levels. The multiple combinations of equatorial and axial ligands explored in this work, allowed us to conclude that octahedral Pt (IV) compounds containing tridentate [C,N,N'] ligands are the optimal design to improve efficacy and selectivity against cancer cell lines. Remarkably, we have also identified that these novel cyclometallated Pt (IV) exhibit a complete absence of cross-resistance with the platinum-resistant CRC and CRPC models generated in this work.Indeed, platinum-based chemotherapy can severely affect internal cell architecture, causing fluctuations in the levels of macromolecular crowding inside cells and having an impact on the supramolecular organization of cell metabolism. In turn, this has been proved to have a profound impact on the kinetic behavior of metabolic enzymes that govern the rate of metabolic pathways that we have identified as important throughout this work.Thus, we have explored the kinetic behavior of lactate dehydrogenase (LDH), as a representative of aerobic glycolysis, under the presence of globular obstacles that do not introduce specific interactions with either LDH or its substrates, dextran polymers, obtaining that LDH kinetics is impaired in an obstacle size- and concentration-dependent manner. Additionally, we unveiled that LDH kinetic behavior shifts from activation control to diffusion control as crowding increases, implying that the behavior of LDH inside cells could be significantly different than previous dilute solution kinetic studies of this enzyme had predicted. On the other hand, the effect of macromolecular crowding on glutaminolysis had not been explored prior to this work. By studying the kinetic behavior of glutamate dehydrogenase (GLDH) in crowded media and characterizing its negative cooperativity, we have concluded that its kinetics is impaired by crowding in an obstacle size- and concentration-dependent manner, but that negative cooperativity is not significantly altered by macromolecular crowding. The actual impact of macromolecular crowding on cell metabolism has been scarcely explored and we are just scratching the surface of the understanding of the multiple implications that this phenomenon may entail for cell physiology and, in particular, for the metabolic alterations of cancer cells. Our observations throughout this work will hopefully have contributed to set grounds onto this enthralling enterprise, as long as meaningfully contributed to encounter valuable therapeutic tools against metastatic CRPC and CRC that can circumvent platinum resistance, both with new generations of platinum compounds and novel metabolic targets that selectively target metastatic solid tumors." -- TDX.
Tumor Cell Metabolism
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Author : Sybille Mazurek
language : en
Publisher: Springer
Release Date : 2015-01-19
Tumor Cell Metabolism written by Sybille Mazurek and has been published by Springer this book supported file pdf, txt, epub, kindle and other format this book has been release on 2015-01-19 with Medical categories.
The four sections of this book cover cell and molecular biology of tumor metabolism, metabolites, tumor microenvironment, diagnostics and epigenetics. Written by international experts, it provides a thorough insight into and understanding of tumor cell metabolism and its role in tumor biology. The book is intended for scientists in cancer cell and molecular biology, scientists in drug and diagnostic development, as well as for clinicians and oncologists.
Technological And Medical Implications Of Metabolic Control Analysis
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Author : Athel Cornish-Bowden
language : en
Publisher: Springer Science & Business Media
Release Date : 2012-12-06
Technological And Medical Implications Of Metabolic Control Analysis written by Athel Cornish-Bowden and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2012-12-06 with Medical categories.
Two decades have passed since the mechanisms of protein synthesis became well enough understood to permit the genetic modification oforganisms. An impressive amount of new knowledge has emerged from the new technology, but much ofthe promise of20years ago has notyet been fulfilled. In biotechnology, efforts to increase the yields of commercially valuable metabolites have been less successful than ex pected, and when they have succeeded it has often been as much from selective breeding as from new methods. The cell is more complicated than what is presented in the classical teaching of biochemistry, it contains more structure than was dreamed of 20 years ago, and the behaviour ofany systemofenzymes is more elaborate than can be explained in terms ofa single supposedly rate-limiting enzyme. Even if classical enzymology and meta bolism may have seemed rather unfashionable during the rise ofmolecular biology, they remain central to any modification ofthe metabolic behaviour oforganisms. As such modification is essential in much ofbiotechnology and drug development, bio technologists can only ignore these topics at their peril.
Cumulated Index Medicus
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Author :
language : en
Publisher:
Release Date : 1997
Cumulated Index Medicus written by and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 1997 with Medicine categories.
Dynamics Of Bone And Cartilage Metabolism
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Author : Markus J. Seibel
language : en
Publisher: Elsevier
Release Date : 2006-07-24
Dynamics Of Bone And Cartilage Metabolism written by Markus J. Seibel and has been published by Elsevier this book supported file pdf, txt, epub, kindle and other format this book has been release on 2006-07-24 with Medical categories.
This updated edition is a comprehensive treatise that spans the complete range of basic biochemistry of bone and cartilage components to the clinical evaluation of disease markers in bone and joint disorders. With contributions from over 75 international experts, Dynamics of Bone and Cartilage Metabolism, Second Edition, is indispensable reading for those involved in skeletal research as well as for rheumatologists, endocrinologists, clinical biochemists, and other clinical disciplines participating in the management of patients with bone and cartilage diseases. Part I provides an up-to-date account of current knowledge of the structure, biosynthesis and molecular biology of the major tissue components Part II covers the organizational structure and cellular metabolism of bone and cartilage Part III deals with the utility of components specific to bone and cartilage as biomarkers of health and disease
Sphingolipid Metabolism And Cell Signaling Part B
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Author :
language : en
Publisher: Elsevier
Release Date : 2000-10-25
Sphingolipid Metabolism And Cell Signaling Part B written by and has been published by Elsevier this book supported file pdf, txt, epub, kindle and other format this book has been release on 2000-10-25 with Science categories.
This volume contains information on analyzing sphingolipids, sphingolipid transport and trafficking, and sphingolipid-protein interactions and cellular targets. Its companion Volume 311 presents methods used in studying enzymes of sphingolipid biosynthesis and turnover, including inhibitors of some of these enzymes, genetic approaches, and organic and enzymatic syntheses of sphingolipids and analogs. The critically acclaimed laboratory standard for more than forty years, Methods in Enzymology is one of the most highly respected publications in the field of biochemistry. Since 1955, each volume has been eagerly awaited, frequently consulted, and praised by researchers and reviewers alike. Now with more than 300 volumes (all of them still in print), the series contains much material still relevant today--truly an essential publication for researchers in all fields of life sciences.
Aggregation Induced Emission Aie
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Author : Jianwei Xu
language : en
Publisher: Elsevier
Release Date : 2022-04-17
Aggregation Induced Emission Aie written by Jianwei Xu and has been published by Elsevier this book supported file pdf, txt, epub, kindle and other format this book has been release on 2022-04-17 with Technology & Engineering categories.
Aggregation-Induced Emission (AIE): A Practical Guide introduces readers to the topic, guiding them through fundamental concepts and the latest advances in applications. The book covers concepts, principles and working mechanisms of AIE in AIE-active luminogens, with different classes of AIE luminogens reviewed, including polymers, three-dimensional frameworks (MOFs and COFs) and supramolecular gels. Special focus is given to the structure-property relationship, structural design strategies, targeted properties and application performance. The book provides readers with a deep understanding, not only on the fundamental principles of AIE, but more importantly, on how AIE luminogens and AIE properties can be incorporated in material development. Provides the fundamental principles, design and synthesis strategies of aggregation induced emission materials Reviews the most relevant applications in materials design for stimuli-responsive materials, biomedical applications, chemo-sensing and optoelectronics Emphasizes structural design and its connection to aggregation induced emission properties, also exploring the structure-property relationship
Exploring Cancer Metabolic Reprogramming Through Molecular Imaging
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Author : Franca Podo
language : en
Publisher: Frontiers Media SA
Release Date : 2017-07-27
Exploring Cancer Metabolic Reprogramming Through Molecular Imaging written by Franca Podo and has been published by Frontiers Media SA this book supported file pdf, txt, epub, kindle and other format this book has been release on 2017-07-27 with Cancer categories.
The inclusion of oncogene-driven reprogramming of energy metabolism within the list of cancer hallmarks (Hanahan and Weinberg, Cell 2000, 2011) has provided major impetus to further investigate the existence of a much wider metabolic rewiring in cancer cells, which not only includes deregulated cellular bioenergetics, but also encompasses multiple links with a more comprehensive network of altered biochemical pathways. This network is currently held responsible for redirecting carbon and phosphorus fluxes through the biosynthesis of nucleotides, amino acids, lipids and phospholipids and for the production of second messengers essential to cancer cells growth, survival and invasiveness in the hostile tumor environment. The capability to develop such a concerted rewiring of biochemical pathways is a versatile tool adopted by cancer cells to counteract the host defense and eventually resist the attack of anticancer treatments. Integrated efforts elucidating key mechanisms underlying this complex cancer metabolic reprogramming have led to the identification of new signatures of malignancy that are providing a strong foundation for improving cancer diagnosis and monitoring tumor response to therapy using appropriate molecular imaging approaches. In particular, the recent evolution of positron emission tomography (PET), magnetic resonance spectroscopy (MRS), spectroscopic imaging (MRSI), functional MR imaging (fMRI) and optical imaging technologies, combined with complementary cellular imaging approaches, have created new ways to explore and monitor the effects of metabolic reprogramming in cancer at clinical and preclinical levels. Thus, the progress of high-tech engineering and molecular imaging technologies, combined with new generation genomic, proteomic and phosphoproteomic methods, can significantly improve the clinical effectiveness of image-based interventions in cancer and provide novel insights to design and validate new targeted therapies. The Frontiers in Oncology Research Topic “Exploring Cancer Metabolic Reprogramming Through Molecular Imaging” focusses on current achievements, challenges and needs in the application of molecular imaging methods to explore cancer metabolic reprogramming, and evaluate its potential impact on clinical decisions and patient outcome. A series of reviews and perspective articles, along with original research contributions on humans and on preclinical models have been concertedly included in the Topic to build an open forum on perspectives, present needs and future challenges of this cutting-edge research area.
The Metabolic Molecular Bases Of Inherited Disease
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Author :
language : en
Publisher:
Release Date : 2001
The Metabolic Molecular Bases Of Inherited Disease written by and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2001 with Genetic disorders categories.
Double Edged Swords Genetic Factors That Influence The Pathogenesis Of Both Metabolic Disease And Cancer
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Author : Che-Pei Kung
language : en
Publisher: Frontiers Media SA
Release Date : 2019-09-23
Double Edged Swords Genetic Factors That Influence The Pathogenesis Of Both Metabolic Disease And Cancer written by Che-Pei Kung and has been published by Frontiers Media SA this book supported file pdf, txt, epub, kindle and other format this book has been release on 2019-09-23 with categories.
Metabolic diseases and cancers account for half of all mortalities in the world, underscoring the significance of understanding the etiology of these diseases and developing effective therapies. Genomic research in the 21st century has brought cancer and metabolic disease, two once seemingly parallel ailments, as close to each other as they’ve ever been. Many genetic factors have been found to display functions regulating both cancer and metabolic disease. In this research topic: "Double-edged Swords: Genetic Factors That Influence The Pathogenesis of Both MetabolicDisease and Cancer", you will be introduced to individual genes, as well as genetic pathways that play important roles in influencing the progression of both metabolic disease and cancer. By no means covering an exhaustive list of genes qualified, this collection of articles rather serves as a precursor of what is yet to come in biomedical research. It paints the big picture of one of the major fields contributing to the future of “precision medicine”.